Due to the opposite orientation of AF10 and MLL on their respective chromosome arms, MLL-AF10 gene fusion requires complex rearrangements with three or more breakpoints. An inversion of the 5'MLL or 3'AF10 is required in order to allow an in-frame MLL-AF10 fusion.

Hybrid/Mutated Gene

5' MLL - 3' AF10; breakpoints are at variable places along AF10

Abnormal Protein

The AF10 Ext-LAP/PHD is always deleted, as are the MLL PHD fingers. Both retain the C-term LZ domain necessary for malignant transformation.

Present both in myeloid and non myeloid acute leukemias: in T-cell ALL specific to TCRgd lineage; in myeloid leukemia described in FAB M0-AML, M1-AML, M5-AML, M7-AML.

Prognosis

poor

Cytogenetics

may well be confused with the above t(10;11)(p12;q23)

Hybrid/Mutated Gene

5' CALM - 3' AF10 and 5' AF10 - 3' CALM In a 5' breakpoint cluster region (nucleotides 424 and 589), AF10 sequences retained the Ext-LAP/PHD domain. The presence of these kind of sequences seems to be necessary for maturation toward the TCRgd lineage, whereas their absence leads to maturation arrest at a more immature stage.

Abnormal Protein

both CALM-AF10 and the reciprocal AF10-CALM are expressed. However, the CALM-AF10 contains most of the functional domains present in each of the two proteins.

Breakpoints

Note

the breakpoint in the t(10;11)(p13;q14-21) is more in 5' of AF10

Bibliography

CALM-AF10 is a common fusion transcript in T-ALL and is specific to the TCRgammadelta lineage.